title: A tomato lycopene complex protects the kidney from cisplatin-induced injury via affecting oxidative stress as well as Bax, Bcl-2, and HSPs expression.
abstract: Cisplatin-induced nephrotoxicity is related to an increase in oxidative stress in the kidney. Lycopene, a carotenoid found in tomatoes, is a potent dietary antioxidant. In the present study, we investigated the effect of the tomato lycopene complex against cisplatin-induced lipid peroxidation and nephrotoxicity in rats. Male Wistar rats (n = 28, 8 wk old, between 200-215 g) were divided into 4 groups: (a) control, (b) tomato lycopene complex (6 mg/kg, daily; consisting of 6% lycopene, 1.5% tocopherols, 1% phytoene and phytofluene, and 0.2% β-carotene), (c) cisplatin (7 mg/kg i.p., single dose), and (d) cisplatin + tomato lycopene complex. Cisplatin administration increased serum urea-N (171 vs. 37 mg/dl) and creatinine (1.80 vs. 0.42 mg/dl) and decreased body weight in comparison with the control rats (P < 0.001). Serum creatinine and urea-N levels were lower in rats treated with tomato lycopene complex + cisplatin compared with rats treated with cisplatin alone (P < 0.001). The renal tissue from the cisplatin-treated rats had greater malondialdehyde (MDA; 172 vs. 93 nmol/g) and 8-isoprostane levels (1810 vs. 610 pg/g) than that from the control rats (P < 0.001). Tomato lycopene complex prevented the rise of MDA and 8-isoprostane (P < 0.001). No measurable lycopene could be detected in the serum of the control and cisplatin-treated rats, whereas lycopene was observed in the serum of rats supplemented with tomato lycopene complex. Renal Bax protein expression was significantly higher in the cisplatin-treated rats than in the control rats, and tomato lycopene complex treatment significantly reduced Bax expression (P < 0.001). The expression of Bcl-2 was higher in tomato lycopene complex/cisplatin-treated rats than in the cisplatin-injected rats (P < 0.05). The expression of renal HSP60 and HSP70 was significantly lower in tomato lycopene complex + cisplatin-treated rats than in rats treated with cisplatin alone (P < 0.001). These results suggest that tomato lycopene complex has protective effects against cisplatin-induced nephrotoxicity and lipid peroxidation in rats.
authors.affiliation: Department of Nephrology, School of Medicine, Firat University, Elazig, Turkey.
authors.forename: Ayhan
authors.initials: A
authors.lastname: Dogukan
authors.forename: Mehmet
authors.initials: M
authors.lastname: Tuzcu
authors.forename: Can Ali
authors.initials: CA
authors.lastname: Agca
authors.forename: Hasan
authors.initials: H
authors.lastname: Gencoglu
authors.forename: Nurhan
authors.initials: N
authors.lastname: Sahin
authors.forename: Muhittin
authors.initials: M
authors.lastname: Onderci
authors.forename: Ibrahim Hanifi
authors.initials: IH
authors.lastname: Ozercan
authors.forename: Necip
authors.initials: N
authors.lastname: Ilhan
authors.forename: Omer
authors.initials: O
authors.lastname: Kucuk
authors.forename: Kazim
authors.initials: K
authors.lastname: Sahin
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001806:Blood Urea Nitrogen; D002338:Carotenoids / Q000494:pharmacology*; D002945:Cisplatin / Q000633:toxicity; D015237:Dinoprost / Q000031:analogs & derivatives / Q000032:analysis; D015536:Down-Regulation; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D000077276:Lycopene; D018551:Solanum lycopersicum / Q000737:chemistry*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D018384:Oxidative Stress / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D024505:Tocopherols / Q000494:pharmacology; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*; D019207:beta Carotene / Q000494:pharmacology
chemical_list: D000975:Antioxidants; C494828:Bax protein, rat; D006360:Heat-Shock Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019207:beta Carotene; C075750:8-epi-prostaglandin F2alpha; D002338:Carotenoids; D008315:Malondialdehyde; C003140:phytofluene; C100185:(all-E) phytoene; D015237:Dinoprost; D002945:Cisplatin; D024505:Tocopherols; D000077276:Lycopene